Exposure to a severe stress reduces endogenous levels of norepinephrine (NE) in the brain by only a small percentage of the total store. Recent behavioral analyses in this lab reveal that NE neuron function is severely impaired or temporarily abolished by stress-induced transmitter depletion and suggest that perhaps all NE dependent processes may be suspended during the post-stress period. In view of the wide variety of important behavioral and physiological functions subserved by NE neurons which would be compromised during this critical time, this possibility would have great consequence for the animal. Therefore, the experiments proposed here will extend this work. The research plan emphasizes further behavioral testing during the post-stress period when NE neurons exhibit biochemical evidence of impaired functional capabilities. Locus coeruleus self-stimulation and glucoprivic feeding, two NE dependent behaviors, have been chosen for analysis since such behaviors should provide a direct indication of NE neuron function. Effort will be made to determine the specificity of the behavioral defict after stress and its precise relationship to NE neuron biochemistry. In addition, these behaviors will be tested after more selective depletions of hypothalamic or telencephalic NE produced by intense electrical activation of specific ascending NE fiber pathways. Recent experiments in this laboratory have also demonstrated striking age-related differences in the rate of biochemical and behavioral recovery after stress exposure. Additional biochemical and morphological studies are proposed here to investigate the specific cellular basis for these age differences. Activity of the NE-synthesizing enzyme dopamine-B-hydroxylase, rate of formation of catecholamines and metabolites from labeled precursor, and catecholamine concentrations will be measured in major brain regions and in individual hypothalamic nuclei following prolonged hypothermic stress. NE-rich hypothalamic nuclei which are severely altered by stress will be analyzed by electron microscopy in search of morphological correlates of impaired biochemical and synaptic function.